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Transcriptomic effects of combination Menin-MLL1 inhibition and FLT3 inhibition on human AML cells

ABSTRACT: Chromosomal translocations of the MLL1 gene cooccur with the activating mutations in FLT3 kinase in acute myeloid leukemia patients, providing the rationale to explore combination of the menin-MLL1 inhibitor (MI-3454) and FLT3 inhibitor (Gilteritinib) in leukemia models. Here, we pursued global gene expression studies after 7 days of treatment of MOLM13 cells (harboring MLL-AF9 and FLT3-ITD) with MI-3454 and Gilteritinib used as single agents and in combination. We observed that MYC, differentiation and stemness-associated gene programs were disrupted by the single agent treatments, but the effect was enhanced upon combinatorial treatment. These results provide a mechanistic input on the increased activity of MI-3454 when combined with Gilteritinib in leukemia models versus single agent treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149049 | GEO | 2020/12/17

REPOSITORIES: GEO

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